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Nucleic Acids Research Papers Touch on Chromatin Accessibility Prediction, Multiple Gene Editing, More

A Johns Hopkins University team propose a single-cell RNA sequencing strategy for predicting chromatin accessibility and related regulatory element activity in samples with scant numbers of cells available. Starting with RNA-seq and matched DNase-seq data generated for dozens of human cell types in the Roadmap Epigenomics and ENCODE projects, the researchers trained a supervised learning method called BIRD to predict DNase I hypersensitivity based on RNA-seq profiles for bulk samples, samples with small cell numbers, or single cells. As they demonstrated with data for human cell lines, embryonic stem cells, or bone marrow cells, these predictions can provide a window into chromatin accessibility, transcription factor binding sites, and more. From these and other results, the authors suggest that "[p]redictions based on single-cell RNA-seq can more accurately reconstruct bulk chromatin accessibility than using [single-cell ATAC-seq]," though they add that such predictions may be improved by incorporating ATAC-seq clues.

Researchers at the Max Planck Institute for Evolutionary Anthropology describe a potential method for editing multiple genes at the same time using an induced pluripotent stem cell line with an inducible, DNA-nicking version of Cas9 in combination with a mutated version of PRKDC — a gene coding for a component of the DNA-dependent protein kinase complexes found at double-strand breaks when CRISPR nucleases clip DNA that has been targeted by guide RNAs. Such DNA breaks are typically patched up by non-homologous end joining or more accurate homology-directed repair, the team explains. By altering PRKDC, the authors were able to boost homology-directed repair activity, helping to introduce edits in as many as four genes. "The approach … makes it possible to simultaneously edit multiple target genes in a single cell much more efficiently than is currently possible," they suggest.

A team from Wenzhou Medical University, the Chinese Academy of Sciences, and elsewhere present an online public database focused on 5-methylcytosine (5mC) methylation and other epigenetic profiles produced from circulating cell-free DNA (cfDNA). The "cell-free epigenome atlas" (CFEA) currently houses 5mC, 5-hydroxymethylcytosine, and nucleosome position profiles spanning more than two-dozen human diseases, the researchers explain, along with related bioinformatic and visualization tools. To improve cfDNA-based epigenetic analyses of cancer, for example, the authors came up with specialized browsers for samples collected across cancers stages. "Similar to the modification-specific browsers … the cancer stage browser can be searched using a custom combination of six menus, including cancer types, stages, detection methods, matched [genomic DNA] data, matched health data, and interested gene/region," the authors write.